Disease Control Implications of India's Changing Multi-Drug Resistant Tuberculosis Epidemic

Abstract

BackgroundMulti-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment.Methods and FindingsWe developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation.We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission – by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality.ConclusionsAs transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements.

Cost-effectiveness of improvements in diagnosis and treatment accessibility for tuberculosis control in India

“…10 We previously published the model calibration and validation to multiple demographic and epidemiological measures over time, including TB case notification rates, MDR incidence, and MDR prevalence. 9 Additional model description and calibration results appear in the supplemental information (SI). There were no participants in this study and no Ethics Approval Statement applies.…”

“… The remaining model parameters may be found in Suen 2012 9 , where the model was described in detail. ~ * Presumptive Gold Standard * Equivalent to 15% over 8 months, the length of DOTS first line treatment ** Equivalent to probability of default and acquiring MDR TB in public system *** Equivalent to 20% over 3 years. **** Cumulative probabilities of death, default, failure, and success for a complete treatment regimen is given in Table 2 …”

“… The remaining model parameters may be found in Suen 2012 9 , where the model was described in detail. …”

Optimal timing of drug sensitivity testing for patients on first-line tuberculosis treatment

“…Both dynamic compartmental models and individual-level simulations have been used to estimate the effect of disease dynamics in the presence of heterogeneous demographic characteristics [10,11,12,13,14]. These models can be used to quantify the uncertainty around natural disease parameters with scarce data, such as transmission patterns [11].…”

Role of acceptability barriers in delayed diagnosis of Tuberculosis: Literature review from high burden countries

“…Concentration of over 95% of TB-cases/deaths in low and middle-income countries (World Health Organization, 2013b), where suboptimal socioeconomic and demographic environment, coupled with the lack of preventing, diagnostic and treating facilities, create favorable conditions for the spread of disease (World Health Organization, 2013a), demonstrates transition from "treatmentgenerated to transmission-generated MDR-TB" (Andrews et al, 2008;Suen et al, 2014).…”